Viral hepatitis C is an infectious disease of liver acute or chronic inflammation caused by Hepatitis C virus (HCV). The infection of HCV is susceptible to develop into chronic liver diseases, such as chronic hepatitis, liver cirrhosis and liver cancer, and thus seriously affecting people's physical health.
HCV belongs to the Flaviviridae family, and currently can be divided into six genotypes and various subtypes. According to the internationally accepted method, the genotype of HCV is represented by Arabic numerals, and the gene subtype is represented by English lowercase letters, wherein genotype 1 presents a global distribution, and accounts for 70% or more of all the HCV infections, in which the main infection type of Chinese population is HCV 1b subtype. Studies have found that both the 5′- and 3′-ends of the positive strand RNA of HCV contain non-coding region (UTR), and a large multi-protein open reading frame (ORF) is located between UTRs. The ORF encodes a polyprotein precursor of about 3,000 amino acids, which is cleaved into a variety of HCV mature proteins under the combined actions of the signal peptidases encoded by the host and the proteases encoded by HCV. The HCV mature protein comprises four structural proteins and six non-structural proteins, of which the six non-structural proteins are named as NS2, NS3, NS4A, NS4B, NS5A, NS5B, respectively. Studies suggest that the six non-structural proteins play very important roles in the replication of HCV, for example, NS3, in which NS3 serine protease activity can be regulated, and NS5A, which is a phosphorylated protein, contains a interferon sensitivity determining region and has important roles in interferon therapy forecast, viral replication, antiviral resistance, hepatocellular carcinogenesis and other aspects, and has become a research focus for HCV non-structural proteins.
Currently, the treatment method for HCV infection is generally recombinant interferon α alone or a combined therapy of recombinant interferon α with nucleoside analogue ribavirin. However, for either interferon or ribavirin, there are a plurality of contraindications, and the clinical benefit are limited. Therefore, there remains a great demand for drugs which can effectively treat HCV infection.